期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 24, 页码 -出版社
MDPI
DOI: 10.3390/ijms232415733
关键词
MD1003; murine oligodendrocytes; human oligodendrocytes; humanized animal model; shiverer mice; oligodendrocyte differentiation; myelination
资金
- MEDDAY Pharmaceuticals
- Institut National de la Sante (INSERM)
- ICM
- INBS NeurATRIS
- French Multiple Sclerosis Foundation (ARSEP) [ANR-11-INBS-0011]
- ARSEP [1259, ARSEP 1254]
Accumulating evidences suggest a strong correlation between metabolic changes and neurodegeneration in CNS demyelinating diseases such as multiple sclerosis (MS). Biotin or high-dose-biotin (MD1003) has been shown to increase the number and differentiation potential of murine and human oligodendrocytes, but without enhancing their myelination potential.
Accumulating evidences suggest a strong correlation between metabolic changes and neurodegeneration in CNS demyelinating diseases such as multiple sclerosis (MS). Biotin, an essential cofactor for five carboxylases, is expressed by oligodendrocytes and involved in fatty acid synthesis and energy production. The metabolic effect of biotin or high-dose-biotin (MD1003) has been reported on rodent oligodendrocytes in vitro, and in neurodegenerative or demyelinating animal models. However, clinical studies, showed mild or no beneficial effect of MD1003 in amyotrophic lateral sclerosis (ALS) or MS. Here, we took advantage of a mouse model of myelin deficiency to study the effects of MD1003 on the behavior of murine and grafted human oligodendrocytes in vivo. We show that MD1003 increases the number and the differentiation potential of endogenous murine oligodendroglia over time. Moreover, the levels of MD1003 are increased in the plasma and brain of pups born to treated mothers, indicating that MD1003 can pass through the mother's milk. The histological analysis of the grafted animals shows that MD1003 increased proliferation and accelerates differentiation of human oligodendroglia, but without enhancing their myelination potential. These findings provide important insights into the role of MD1003 on murine and human oligodendrocyte maturation/myelination that may explain the mitigated outcome of ALS/MS clinical trials.
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